The long-term goal of these studies is an understanding of how intracellular levels of cyclic GMP are controlled. This will be approached by studying the control of cyclic GMP levels in intact cells and by studying, in cell-free systems, the regulation of the enzymes that are involved in the biosynthesis and degradation of cyclic GMP. Specifically, guanylate cyclase from both soluble and particulate sources will be purified and characterized. Possible direct effects of various hormones, neurotransmitters and cations on purified and crude preparations of the enzyme will be examined along with effects of the same agents on cyclic GMP levels in intact tissues. Cyclic nucleotide phosphodiesterases will be studied directly in purified preparations and indirectly in intact cells in an attempt to establish whether or not forms of the enzyme with selectivity for cyclic GMP and cyclic AMP in cell-free systems have the same selectivity in intact cells and, if so, whether or not these forms can be separately controlled physiologically and pharmacologically. BIBLIOGRAPHIC REFERENCES: Patterson, W. D., Hardman, J. G. and Sutherland, E. W. (1976) Apparent Multiple Forms of Cyclic AMP Phosphodiesterase from Rat Erythrocytes. Mol. Cell. Endocrinol. 5:51-66. Gray, J. P., Drummond, G. I., Luk, D. W. T., Hardman, J. G. and Sutherland, E. W. (1976) Enzymes of Cyclic Nucleotide Metabolism in Invertebrate and Vertebrate Sperm. Arch. Biochem. Biophys. 172:20-30.